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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: -18.4 [2.1]/ -10.6 [1.7] versus -10.4 [1.8]/-5.8 [1.4]; nighttime: -15.6 [2.7]/-8.1 [1.8] versus -8.8 [2.9]/-5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: -10.5 [2.9]/-8.1 [2.1] and -14 [3.7]/-8.7 [2.3] versus -6.1 [2.4]/-5.9 [1.5]; nighttime: -8.1 [2.6]/-5.3 [2.4] and -9.6 [3.4]/-5.3 [2.4] versus -2 [2.3]/-0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: -14.8 [2]/-8.2 [1.3] and -13.3 [1.6]/-6.8 [0.9] versus -11.4 [1.6]/-6.5 [1.1]; nighttime: -16.1 [2.4]/-8.6 [1.7] and -13.2 [2.7]/-7.2 [1.9] versus -9.0 [2.5]/-4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (P<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension.
Hypertension 2007 Feb
PMID:Aliskiren reduces blood pressure and suppresses plasma renin activity in combination with a thiazide diuretic, an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker. 1743 43

Measurement of blood pressure in the clinic may provide a false impression of blood pressure control. Ambulatory blood pressure monitoring (ABPM) allows the automatic recording of the circadian variation in blood pressure and evaluation of the efficacy of antihypertensive medication throughout the dosing interval. Ambulatory blood pressure provides more effective prediction of cardiovascular risk; blood pressure control at the time of heightened risk in the early morning after waking and before taking the next dose of medication is becoming important in order to improve long-term prognosis. To achieve blood pressure control in the early morning, a long-acting antihypertensive agent is essential. Telmisartan, an angiotensin II receptor blocker, as well as having a terminal elimination half-life of 24 h, has a large volume of distribution due to its high lipophilicity. The efficacy of telmisartan 80 mg monotherapy has been demonstrated using ABPM, with superior reduction in mean values for the last 6 h of the dosing interval compared with ramipril 10 mg and valsartan 80 mg. In addition, telmisartan 80 mg provides superior blood pressure control after a missed dose compared with valsartan 160mg. When combined with hydrochlorothiazide (HCTZ) 12.5 mg, telmisartan 40mg and 80mg is more effective than losartan/HCTZ (50/12.5 mg) at the end of the dosing interval. Furthermore, greater reductions in last 6 h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) are achieved with telmisartan/HCTZ (80/12.5 mg) than with valsartan/HCTZ (160/12.5 mg) in obese patients with type 2 diabetes and hypertension. Recent data from a large group of patients show that telmisartan 80 mg controls the early morning blood pressure surge more effectively than ramipril 5-10 mg and, thus, may have a greater beneficial effect on long-term cardiovascular risk. This supposition is being tested in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) programme.
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PMID:A review of telmisartan in the treatment of hypertension: blood pressure control in the early morning hours. 1732 26

Cardiovascular disease represents a continuum that starts with risk factors, such as hypertension, and progresses to atherosclerosis, target organ damage, and ultimately leads to heart failure or stroke. Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with ACE inhibitors in patients with coronary artery disease, but no such data are currently available for ARBs. Both ACE inhibitors and ARBs have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Trials, such as the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND), that compare telmisartan, ramipril, and their combination in high-risk patients with vascular end-organ damage, should provide important new insights into the benefits of intervention with RAS blockade along the cardiorenovascular continuum.
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PMID:Angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors: where do we stand now? 1830 33

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) differ in their actions on the renin-angiotensin-aldosterone system (RAAS). ACE inhibitors prevent the formation of angiotensin II, although angiotensin II may still be generated by alternative pathways. However, ACE inhibitors interrupt bradykinin breakdown, which in turn potentially enhances nitric oxide and prostacyclin mechanisms. In contrast, ARBs selectively prevent the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor while leaving the potentially beneficial effects of the AT(2) receptor unaffected. The supposition is that dual blockade of the RAAS effectively overcomes the harmful effects of angiotensin II mediated by the AT(1) receptor while offering the additional effects of the ACE inhibitor. This concept was first evaluated clinically more than a decade ago in small-scale studies that were not sufficiently powered to conclusively demonstrate benefits from dual blockade. Subsequently, larger-scale trials have been conducted to determine the effects of a combination of an ACE inhibitor and an ARB in combating the effects of angiotensin II at different stages of cardiovascular and renal disease. This review explores these data in areas, such as hypertension, renal disease, and cardiovascular disease, and draws on this preliminary evidence to support the rationale for the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET) program, which aims to fully explore the clinical end points and effects of dual RAAS blockade in patients at high risk for cardiovascular outcomes.
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PMID:New opportunities in cardiovascular patient management: a survey of clinical data on the combination of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. 1766 98

Several studies have questioned the effect of hypertension on cognitive functions. Event related potentials (P300) have been used as a reliable and reproducible indicator of cognitive functions. In this non-randomized, open label study we investigated cognitive functions using event related potentials in newly diagnosed mild to moderate essential hypertensive patients and whether or not there was any effect of antihypertensive treatment with angiotensin converting enzyme inhibitor ramipril on the event related potentials. We selected twenty male patients of newly diagnosed mild to moderate essential hypertension by using ambulatory blood pressure monitoring who were previously untreated and compared their event related potentials with 10 normotensive controls. At the beginning of the study, the hypertensive group showed increased P300 and N2 wave latency as compared to the normotensive control subjects. After three months of Ramipril therapy at a dose of 5mg per day, there was a significant decrease in all the ambulatory blood pressure parameters and the mean P300 latency from the pretreatment values. But no significant change in the N2 latency was observed. Thus, treatment with Ramipril 5 mg daily for a period of three months can reverse some aspects of cognitive dysfunction associated with hypertension.
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PMID:Effect of ramipril therapy on cognitive functions in cases of mild to moderate essential hypertension. 1787 91

The angiotensin receptor blockers (ARBs) are well established as safe and effective in the treatment of arterial hypertension. Telmisartan is an ARB with potent blood-pressure lowering effects. It has a long terminal half-life of about 24 hours (the longest of any of the ARBs), which enables it to sustain blood pressure reductions in the early morning hours, after the previous morning dosing. Unlike the angiotensin-converting enzyme (ACE) inhibitors, the ARBs have not been shown to reduce mortality and morbidity in high-risk patients with coronary disease, peripheral vascular disease, cerebrovascular disease, or diabetes with cardiovascular risk factors without evidence of heart failure or low ejection fraction. Two studies, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE-I INtolerant Subjects with Cardiovascular Disease (TRANSCEND) trial, are examining the benefits of ARBs alone and in combination with ACE inhibitors in high-risk patients.
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PMID:A perspective on telmisartan and cardiovascular risk. 1793 15

Patients with kidney failure are at high risk of a cardiac death and frequently develop left ventricular hypertrophy (LVH). The mechanisms involved in the cardiac structural changes that occur in kidney failure are yet to be fully delineated. Angiotensin-converting enzyme (ACE) 2 is a newly described enzyme that is expressed in the heart and plays an important role in cardiac function. This study assessed whether ACE2 plays a role in the cardiac remodelling that occurs in experimental acute kidney injury (AKI). Sprague-Dawley rats had sham (control) or subtotal nephrectomy surgery (STNx). Control rats received vehicle (n = 10), and STNx rats received the ACE inhibitor (ACEi) ramipril, 1 mg kg(-1) day(-1) (n = 15) or vehicle (n = 13) orally for 10 days after surgery. Rats with AKI had polyuria (P < 0.001), proteinuria (P < 0.001) and hypertension (P < 0.001). Cardiac structural changes were present and characterized by LVH (P < 0.001), fibrosis (P < 0.001) and increased cardiac brain natriuretic peptide (BNP) mRNA (P < 0.01). These changes occurred in association with a significant increase in cardiac ACE2 gene expression (P < 0.01) and ACE2 activity (P < 0.05). Ramipril decreased blood pressure (P < 0.001), LVH (P < 0.001), fibrosis (P < 0.01) and BNP mRNA (P < 0.01). These changes occurred in association with inhibition of cardiac ACE (P < 0.05) and a reduction in cardiac ACE2 activity (P < 0.01). These data suggest that AKI, even at 10 days, promotes cardiac injury that is characterized by hypertrophy, fibrosis and increased cardiac ACE2. Angiotensin-converting enzyme 2, by promoting the production of the antifibrotic peptide angiotensin(1-7), may have a cardioprotective role in AKI, particularly since amelioration of adverse cardiac effects with ACE inhibition was associated with normalization of cardiac ACE2 activity.
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PMID:Acute kidney injury in the rat causes cardiac remodelling and increases angiotensin-converting enzyme 2 expression. 1822 26

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.
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PMID:Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for reduction of adverse cardiovascular events in patients with diabetes mellitus and preserved left ventricular function. 1832 70

Angiotensin-converting enzyme inhibitors combined with higher doses of hydrochlorothiazide (HCT), that is, 25 mg daily, have been recognized as an effective form of antihypertensive therapy. To evaluate the coadministration of 20 mg ramipril with 25 mg HCT, we carried out a randomized, double-blind, controlled trial with two dose schedules of ramipril (20 mg q.d. and 10 mg b.i.d.) and HCT monotherapy arms as comparators in 354 patients with stage 2 hypertension. The clinic blood pressure (BP) was assessed using a semiautomatic digital device and 24-h BP was measured using ambulatory BP recordings at baseline and after 8 weeks of therapy. At baseline, the demographics and baseline BP values were similar in the four treatment groups (age: 51-53 years, 52-58% male, 64-68% non-black, clinic BP: 155-158/103-104 mm Hg). Ramipril-HCT induced significantly greater reductions in both the clinic and ambulatory BP than the HCT and ramipril monotherapy treatments (for example, additional reductions in ambulatory BP on ramipril-HCT ranged from -7.3/-5.2 to -10.3/-7.4 mm Hg compared to the monotherapies, all P<0.001). Reductions from baseline were still numerically greater for the clinic BPs derived from device measurements than those for the BP values derived from 24-h ambulatory BP measurements (changes in clinic diastolic BP ranged from -8.5 to -15.5 mm Hg across treatment groups, whereas changes in ambulatory diastolic BP were -4.7 to -12.0 mm Hg for the same groups). Thus, these data support the use of ambulatory BP monitoring even when automated BP devices are used for the assessment of clinical BP in trials that attempt to differentiate BP responses among active comparator groups. In conclusion, based on its efficacy and tolerability profile the combination of ramipril and HCT was shown to be effective therapy for the treatment of stage 2 hypertension.
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PMID:Utility of semiautomatic clinic and 24-h ambulatory blood pressure measurements to evaluate combination therapy: the Ramipril-Hydrochlorothiazide Hypertension trial. 1846 72

The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in blood pressure regulation and hypertension-related complications. Angiotensin-converting enzyme inhibitors (ACEIs) were the first to be used to block the RAAS and now have many compelling indications in the treatment of hypertension and its cardiovascular and renal complications. Angiotensin II receptor blockers (ARBs), introduced 20 years later, have been shown to be equally as effective as antihypertensive treatment and are also associated with a lower number of side effects. Furthermore, in clinical trials ARBs and ACEIs were associated with comparable benefits for their most typical indications. This was confirmed in the 2007 New European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension by comparable specific recommendations for ARB and ACEI treatment. There is sufficient theoretical background and, in some cases, also clinical evidence that combination therapy with ACEIs and ARBs may be more beneficial than monotherapy with either of the groups alone, both in uncomplicated hypertension and with concomitant heart failure or renal dysfunction. However, the combination of ACEI and ARB was not recommended in the ESH/ESC 2007 Guidelines. This may change after the publication of the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) study, the preliminary results of which have just been presented. In heart failure, recent studies have shown that the combination of ACEI and ARB decreases cardiovascular mortality and the number of hospitalizations due to aggravation of heart failure. These results have been reflected in the newest ESC guidelines of the heart failure treatment. Nephroprotective properties of the combination of ACEs and ARBs have been proved both in studies on nondiabetic and diabetic nephropathy. The potential benefits, indications in prespecified groups of patients, the most recent data from clinical trials and latest research regarding dual blockade of RAAS will be reviewed in this article.
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PMID:Current possibilities of ACE inhibitor and ARB combination in arterial hypertension and its complications. 1851 Apr 91


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